温肾咳喘片主要成分对HepG2细胞中CYP相关基因表达的影响

张小梅, 冯毅凡, 陈耕夫, 石忠峰

中国生物化学与分子生物学报 ›› 2012, Vol. 28 ›› Issue (1) : 79-85.

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中国生物化学与分子生物学报 ›› 2012, Vol. 28 ›› Issue (1) : 79-85.
研究论文

温肾咳喘片主要成分对HepG2细胞中CYP相关基因表达的影响

  • 张小梅1),冯毅凡1),陈耕夫2),石忠峰1)*
作者信息 +

Effect of Five Components of Wenshen Kechuan Tablet on CYP Related Gene Expression in HepG2 Cells

  • ZHANG XiaoMei1), FENG Yi-Fan1), CHEN Geng-Fu2), SHI Zhong-Feng1)*
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文章历史 +

摘要

观察温肾咳喘片组方中5种主要单体成分甘草酸、厚朴酚、和厚朴酚、蛇床子素和 欧前胡素对细胞色素P450(cytochrome P450, CYP) 1A2,2D6,2E1和3A4基因表达的影 响. 采用实时荧光定量PCR技术检测HepG2细胞中药物处理后各CYP mRNA的表达.厚朴酚 、和厚朴酚、蛇床子素和欧前胡素在不同浓度均能明显的诱导CYP2E1和CYP3A4,同时欧 前胡素也能诱导CYP1A2的表达,而甘草酸、厚朴酚、和厚朴酚、蛇床子素和欧前胡素在 不同浓度对CYP2D6的表达均具有较弱的抑制作用.甘草酸、厚朴酚、和厚朴酚、蛇床子 素和欧前胡素能明显影响CYP1A2、2D6、2E1或3A4的表达.此研究为中西药物代谢性相互 作用及毒理学的研究提供实验依据.

Abstract

The application of botanical supplements or herbal medicinal products with synthetic drugs that are cytochrome P450 enzyme substrates may induce significant herb-drug interaction and may alter pharmacotherapy. In this study, we have investigated potential influence of the five bioactive compounts of Wenshenkechuan tablet on cytochrome P450 enzyme(CYP)1A2, 2D6, 2E1 and 3A4 mRNA expression. The mRNA expression levels of four CYP enzymes were determined by real-time quantitative PCR using specific target primers for P450 genes. The results demonstrated that magnolol, honokiol, osthole and imperatorin induced CYP2E1 and CYP3A4 at different concentrations. And imperatorin also induced CYP1A2 at different concentrations. However, the level of CYP2D6 expression could be decreased by glycyrrhizic acid, magnolol, honokiol, osthole and imperatorin at the different concentrations. The level of CYP expression could be significantly induced or inhibited by glycyrrhizic acid, magnolol, honokiol, osthole and imperatorin. The results could supply the evidence for the interaction of herbdrug based on cytochrome P450 and toxicity, so cares should be taken when glycyrrhizic acid, magnolol, honokiol, osthole and imperatorin are co-administered with other drugs.

关键词

温肾咳喘片 / 细胞色素P450 / 实时荧光定量PCR / 药物相互作用

Key words

Wenshenkechuan tablet / cytochromae P450 / real-time quantitative PCR / herb-drug interaction

引用本文

导出引用
张小梅, 冯毅凡, 陈耕夫, 石忠峰. 温肾咳喘片主要成分对HepG2细胞中CYP相关基因表达的影响[J]. 中国生物化学与分子生物学报, 2012, 28(1): 79-85
ZHANG Xiao-Mei, FENG Yi-Fan, CHEN Geng-Fu, SHI Zhong-Feng. Effect of Five Components of Wenshen Kechuan Tablet on CYP Related Gene Expression in HepG2 Cells[J]. Chinese Journal of Biochemistry and Molecular Biology, 2012, 28(1): 79-85
中图分类号: Q599   

参考文献

[1] Borrelli F, Izzo A A. Herb-drug interaction with St John’s wort (Hypericum perforatum): an update on clinical observation[J]. AAPS J, 2009,11(4):710-727
[2] Gurley B J, Gardner S F, Hubbard M A, et al. Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotype in the elderly: St John’s wort, garlic oil,Panax ginseng and Ginkgo biloba[J]. Drugs Aging, 2005, 22(6): 525-539
[3] Saxena A, Tripathi K P, Roy S, et al. Pharmacovigilance: effects of herbal components on human drugs interactions involving cytrochrome P450[J]. Bioinformation,2008,3(5):198-204
[4] 赵学军,李卫民,熊天琴,等. 温肾咳喘片组分的正交法优选及其主要药效学实验研究[J]. 成都中医药大学学报(Zhao Xue-Jun, Li Wei-Ming, Xiong Tian-Qin, et al. Study of preferred orthogonal of Wenshen Kechuan tablet and its main pharmacodynamic[J]. J Chengdu Univ Tradit Chin Med), 2005,28(1):56-59
[5] 赵学军,李卫民,蔡健聪,等. 温肾咳喘片的主要药效及机制研究[J]. 中药新药与临床药理(Zhao Xue-Jun,Li Wei-Ming, Chai Jian-Cong, et al.A study on the main pharmacodynamic effect of Wenshen Kechuan tablet and its metabolism[J]. Tradit Chin Drug Res Chin Pharmacol), 2006,17(1):25-28
[6] 于叶玲,崔久峰,唐星. HPLC法测定温肾咳喘片中欧前胡素、蛇床子素、和厚朴酚、厚朴酚和甘草酸[J]. 中草药(Yu Ye-Ling, Cui Jiu-Feng, Tang Xing. High-performance liquid chromatography for quantification of imperatorin, osthole, honokiol, magnolol and glycyrrhizic acid of Wenshen Kechuan Tablet[J].Chin Tradit Herb Drugs),2007,38(3):387- 389
[7] 冯毅凡,郭晓玲,孟青,等 温肾咳喘片中五种主要成分的同时测定[J]. 南方医科大学学报(Feng Yi-Fan, Guo Xiao-Ling, Meng Qing, et al. High-performance liquid chromatography for quantification of 5 major components in Wehshenpingchuan tablet by together[J]. J Southern Med Univ),2006,26(12):1782-1784
[8] Livak K J, Schmittgen T D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method[J]. Methods, 2001, 25(4):402-408
[9] Cui X, Thomas A, Han Y, et al. Quantitative PCR assay for cytochromes P450 2B and 3A induction in rat precision-cut liver slices: correlation study with induction in vivo[J]. J Pharmacol Toxicol Methods, 2005, 52(2): 234-243
[10] Martignoni M, de Kanter R, Grossi P, et al. An in vivo and in vitro comparison of CYP gene induction in mice using liver slices and quantitative RT-PCR[J]. Toxicol In Vitro, 2006, 20(1): 125-131
[11] Deng Y, Bi H C, Zhao L Z, et al. Induction of cytochrome P450 3A by the Ginkgo biloba extract and bilobalides in human and rat primary hepatocytes[J]. Drug Metab Lett,2008, 2(1):60-66
[12] Lobo E D, Bergstrom R F, Reddy S, et al. In vitro and in vivo evaluations of cytochrome P450 1A2 interactions with duloxetine[J]. Clin Pharmacokinet, 2008, 47(3):191-202
[13] Mugundu G M,Hariparsad N,Desai P B. Impact of ritonavir, atazanavir and their combination on the CYP3A4 induction potential of efavirenz in primary human hepaatocytes[J]. Drug Metab Lett,2010,4(1):45-50
[14] Sparfel L, Payen L, Gilot D, et al. Pregnant X receptor-dependent and -independent effect of 2-acetylaminofluorene on cytochrome P450 3A23 expression and liver cell proliferation[J]. Biochem Biophys Res Commun,2003,300(2):278-284
[15] Volotinen M, Maenpaa J, Kankuri E, et al. Expression of cytochrome P450(CYP) enzyme in human nonpigmented ciliary epithelial cell: induction of CYP1B1 expression by TCDD[J]. Invest Ophthalmol Vis Sci, 2009, 50(7): 3099-3105
[16] Westerink W M, Schoonen W G. Cytichrome P450 enzyme levels in HepG2 cells and cryopreserved primary human hepatocytes and their induction in HepG2 cells[J]. Toxicol In Vitro, 2007,21(8):1581-1591
[17] Elizondo G, Medina-Diaz I M. Induction of CYP3A4 by 1alpha, 25-dyhydroxyvitamin D3 in HepG2 cells [J]. Life Sci, 2003,73(2):141-149
[18] Brandon E F, Meijerman I, Klijin J S, et al. In-vitro cytotoxicity of ET-743(Trebectedin, Yondelis), a marine anti-cancer drug, in the HepG2 cell line: influence of cytochrome P450 and phase Ⅱ inhibition, and cytochrome P450 induction [J]. Anticancer Drugs, 2005,16(9): 935-943
[19] EI Gendy M A, EI-Kadi A O. Pegnanum harmala L. differently modulates cytochrome P450 gene expression in human hepatoma HepG2 cells [J]. Drug Metab Lett, 2009,3(4):212-216
[20] Honkakoski P, Negishi M. Regulation of cytochrome P450(CYP) genes by nuclear receptors [J]. Biochem J, 2000, 347(pt2):321-337
[21] Fuhr U. Induction of drug metabolizing enzymes: pharmacokinetic and toxicological consequence in humans[J]. Clin Pharmacokinet, 2000,38(6):493-504
[22] Quan J, Yin X, Xu H. Boschniakia rossica prevents the carbon tetrachloride-induced hepatoxicity in rat[J]. Exp Toxicol Pathol, 2011,63(1-2):53-59
[23] Waluga M, Hartleb M. Alcoholic liver disease[J]. Wiad Lek, 2003,56(1-2):61-70
[24] Zhang J, Xue J, Wang H, et al. Osthole improves alcohol-induced fatty liver in mice by reduction by hepatic oxidative stress[J]. Phytother Res, 2011,25(5):638-643
[25] 王宇光,杨明会,马增春,等.18β-甘草酸和18α-甘草酸对大鼠原代肝细胞CYP3A4酶表达的影响 [J],中国中药杂志(Wang Y, Yang M, Ma Z, et al.Effect of 18β-glycyrrhizic acid and 18α-glycyrrhizic acid on mRNA and protein expression of cytochrome P450 3A in cultured rat primary hepatocyte [J]. China J Chin Mater Med), 2009, 34(3):307-311

基金

国家自然科学基金项目(No. 30801543)

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